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Dynamin 2 mediates PDGFRα-SHP-2-promoted glioblastoma growth and invasion

H Feng1, K W Liu, P Guo

  • 1University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863, USA.

Oncogene
|October 15, 2011
PubMed

Insights

Dynamin 2 (Dyn2) is a key player downstream of PDGFRα signaling, mediating glioma cell migration and tumor growth. Targeting the PDGFRα-SHP-2-Dyn2 pathway may offer new glioblastoma treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Receptor tyrosine kinases (RTKs) promote cell migration, but Dyn2's role is unclear.
  • SHP-2 and PI3K mediate PDGFRα-driven glioma growth and invasion.

Purpose of the Study:

  • To elucidate the molecular mechanisms of Dyn2 in RTK-induced cell migration.
  • To establish Dyn2 as an effector in PDGFRα-PI3K/SHP-2 signaling in glioma.

Main Methods:

  • Short hairpin RNA (shRNA) depletion of Dyn2.
  • siRNA knockdown of SHP-2.
  • Dominant-negative SHP-2 mutant.
  • Src inhibitors.
  • PDGFRα binding site mutations.

Main Results:

  • Dyn2 depletion inhibited PDGFRα-stimulated signaling, cell migration, survival, and tumor growth.
  • Dyn2 interacts with SHP-2 and PI3K and colocalizes with PDGFRα.
  • SHP-2 inhibition abrogated Dyn2-PDGFRα association and downstream signaling.
  • SHP-2 and Src inhibition/mutation affected Dyn2 phosphorylation and cell migration.

Conclusions:

  • Dyn2 acts as an effector downstream of PDGFRα-PI3K/SHP-2 signaling in glioma.
  • The PDGFRα-SHP-2-Dyn2 pathway is crucial for glioma tumor growth and invasion.
  • Targeting this pathway could be a therapeutic strategy for glioblastomas.

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